Primary objective of the study is to investigate the efficacy of vorinostat in patients suffering from selected histological types of soft tissue sarcoma. Further evaluations relate to the safety and tolerability of vorinostat, its pharmacokinetics (course of plasma concentration over time) and pharmacodynamics (mode of action). Only subjects with advanced, metastatic disease will be included in this trail.

Evaluation of the efficacy of vorinostat on the basis of progression free survival (PFS) up to 1 year after first administration of the IMP. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evaluation of the efficacy of vorinostat on the basis of overall survival up to 1 year after first administration of the IMP. Investigation on pharmacokinetics und pharmacodynamics of vorinostat. Evaluation of safety and tolerability of vorinostat. [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Daily administration of 400mg vorinostat on 28 days (one therapy cycle). Seven days of therapy break between two consecutive cycles.

Drug: Vorinostat

Daily administration of 400mg vorinostat on 28 days (one therapy cycle). Seven days of therapy break between two consecutive cycles.

Detailed Description:

The treatment with vorinostat will be administered daily over 28 days. This period will be referred to as a therapy cycle. Two consecutive therapy cycles will be separated by a 7-days therapy break. In case of a good response and no relevant side effects, the treatment with vorinostat can be continued for up to 1 year after begin of the treatment. If any relevant side effects or intolerability occur, the dose and/or schedule of administration will be modified according to the pre-defined criteria.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients with verified, metastatic soft tissue sarcoma of the following histologies:

Verified relapse or disease progression at study inclusion, i.e. therapeutic failure of the first line therapy with anthracyclines,

Measurable disease according to the RECIST criteria,

Previous systemic therapy of advanced and/or metastatic disease,

An interval of at least 4 weeks since the last surgery, chemotherapy or radiation,

Age over 18,

Following laboratory findings:

ANC ≥ 1.0 x 10³/mm³,

platelets ≥ 100.000/mm³,

hemoglobin ≥ 9 g/dl,

creatinin < 1.5 x ULN (upper limit of normal),

AST and ALT < 2.5 x ULN,

total bilirubin < 1.5 x ULN,

Life expectancy of at least 12 weeks,

Negative pregnancy test,

Consent for an effective contraception during and up to 6 month after the study completion.

Written informed consent,

Ability to understand the goal and the consequences of this trial.

Exclusion Criteria:

Proof of the following histologies:

gastrointestinal stromal tumor (GIST),

malignant mesothelioma,

neuroblastoma,

osteosarcoma,

Ewing's sarcoma/PNET,

Concurrent radio- or chemotherapy,

Participation in another interventional trial within 4 weeks prior to the inclusion,

Previous therapy with another HDAC-inhibitor (e.g. depsipeptide, MS-275, LAQ-824, PXD-101 und valproic acid). Patients, who underwent a therapy with valproic acid for treatment of seizures, can be included after a wash-out period of at least 30 days,

Symptomatic brain metastases, that have not been treated by radiotherapy. The interval between the last radiation and the study inclusion must not be shorter than 30 days,

Previous malignant disease (except for a non-melanoma of the skin and a carcinoma in situ of uterus), unless in complete remission and after the last therapy for at least 5 years,

Ejection fraction < 40 %,

Nursing,

Known allergy against the IMP or drugs with similar chemical structure or additives,

Active hepatitis B and/or C and HIV-infection

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00918489

Locations

Germany

Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tübingen